P1679: HEALTH-RELATED QUALITY OF LIFE IN PATIENTS (PTS) WITH WALDENSTRÖM MACROGLOBULINEMIA (WM) TREATED WITH ZANUBRUTINIB (ZANU) VS IBRUTINIB (IBR): RESULTS FROM THE PHASE 3 ASPEN TRIAL LONG-TERM FOLLOW-UP
Authors: Alessandra Tedeschi, Constantine Tam, Roger Owen, Christian Buske, Véronique Leblond, Meletios A. Dimopoulos, Ramón García-Sanz, Jorge Castillo, Judith Trotman, Steven Treon, Keri Yang, Boxiong Tang, Heather Allewelt, Sheel Patel, Wai Chan, Aileen Cohen, Jingjing Yan Schneider, Gisoo Barnes
Journal: HemaSphere (2023)

Topic: 35. Quality of life and palliative care Background: ASPEN (NCT03053440) is a randomized, open-label, phase 3 study comparing ZANU, a next-generation potent and selective Bruton tyrosine kinase inhibitor, with IBR in pts with WM. Aims: Health-related quality of life (HRQoL) outcomes were evaluated in Cohort 1 (pts with activating mutations in MYD88) in both the intention-to-treat (ITT) population and pts achieving a complete response or very good partial response (CR + VGPR). Methods: Patient-reported outcomes (PROs) were exploratory endpoints assessed using the EORTC QLQ-C30 and EQ-5D-5L VAS scores. Patients in Cohort 1 completed the questionnaires at baseline (Cycle 1, Day 1), every 3 cycles up to Cycle 13, and every 6 cycles thereafter. Each cycle was 28 days for both arms. Descriptive analysis was performed using all the scales. A linear mixed-effects model for repeated measures analysis assessed the differences between arms for PRO endpoints of global health status (GHS), physical and role functioning, and symptoms of fatigue, diarrhea, and nausea/vomiting. Key clinical cycles in ITT and VGPR populations (pts who achieved a VGPR by Cycle 25) included Cycles 4, 7, 13, and 25; key cycles corresponded to the median times to major response. Clinically meaningful difference was defined as ≥5 points difference from baseline. Results: Overall, 201 pts (102 ZANU; 99 IBR) were enrolled in Cohort 1. Baseline characteristics were similar between arms except for pts aged >75 years (33.3% vs 22.2%), and pts with anemia (hemoglobin ≤110 g/L, 65.7% vs 53.5%) in the ZANU vs IBR arms, respectively. Adverse events (AEs) leading to dose holds or reductions, drug discontinuation, and deaths were higher in the IBR vs ZANU arm. Compliance rates were high (ZANU: 92%–97%; IBR: 89%–98%). In the ITT population, diarrhea, and nausea/vomiting symptom scores were stable from baseline through all key clinical cycles in the ZANU arm; pts on IBR experienced worsening of diarrhea and nausea/vomiting from baseline. In other key PRO endpoints, improvements from baseline for both treatments were observed, but were not significantly different (Table). There was no CR. Median time to VGPR was achieved faster in pts on ZANU (8 months [mo]) vs IBR (17 mo) (CR + VGPR response rate: 38.2% vs 25.3% (P=0.0374), respectively; 31 pts on ZANU who were VGPR responders by Cycle 25 had generally better outcomes in PRO endpoints compared with 17 pts on IBR. Among VGPR responders, the differences between arms were clinically meaningful at Cycle 7 for physical functioning (10.42 [95% CI: 0.57, 20.28]; P=0.0387) and fatigue (-11.76 [95% CI: -22.24, -1.28]; P=0.0288); and again at Cycle 25, (10.45 [95% CI: 0.12, 20.79]; P= 0.0476) for physical functioning and (-13.53 [95% CI: -25.00, -2.06]; P=0.0220) fatigue. Pts on IBR had worse outcomes compared with ZANU in Cycle 4 for diarrhea (-19.83 [95% CI: -33.43, -6.24]; P=0.0053) and nausea/vomiting (-10.98 [95%CI: -22.21, 0.24], P=0.0549). Summary/Conclusion: In the ASPEN trial, treatment with ZANU was associated with greater improvements in HRQoL vs IBR in pts with WM and MYD88 mutations. Clinically meaningful differences were observed in diarrhea and nausea/vomiting in both ITT and VGPR populations in earlier cycles of treatment as well as in long-term physical functioning and fatigue in patients achieving VGPR. For pts who achieved a VGPR by Cycle 25, treatment with ZANU compared with IBR led to an earlier and lasting improvement of HRQoL, consistent with a shorter median time to VGPR.Keywords: Patient reported outcomes, Waldenstrom's macroglobulinemia, Quality of life